# Project 1: Age-related impact on early life B cell lineage-designed SOSIP HIV Env vaccination

> **NIH NIH P01** · DUKE UNIVERSITY · 2020 · $244,720

## Abstract

ABSTRACT – Project 1
There is a critical need to protect adolescents and young adults from HIV infection through the development of
an early life vaccine strategy that elicits protective immunity prior to sexual debut. However, to date, efforts to
develop a vaccine that can elicit protective broadly neutralizing antibodies (bnAbs) have been challenged both
by limited engagement of bnAb epitopes by germline B cell receptors and levels of somatic hypermutation
needed for achievement of bnAb, as well as the likely need for long term boosting and several years time to
evolve the B cell responses towards broad neutralization. Two recent findings suggest that the low risk of HIV
acquisition in the period between breastfeeding and sexual debut might provide unique window and immune
landscape for vaccine-induced bnAb production: 1) the high capacity of the pediatric immune system over that
of adults for the development of bnAb responses during HIV infection, and 2) the remarkably low somatic
hypermutation level in bnAbs isolated from HIV-infected children, which may provide the opportunity to direct
development of bnAb B cell clones through vaccination. Yet, there is a gap in our understanding of the
potential advantages of the early life immune system over that of adults for induction of bnAbs via vaccination.
Thus, Project 1 proposes to compare immune response to long-term immunization with the bnAb germline-
targeting native-like HIV Env trimer: BG505 GT1.1 SOSIP trimer immunogen initiated in infancy compared to
that of pre-adolescents (as well as comparison to BG505 Env mRNA infant vaccination in Project 2).
Specifically, Aim 1 of this project will test the hypothesis that the unique flexibility of the early life immune
system and differential B cell tolerance mechanisms will allow enhanced engagement and evolution of B cell
clones through bnAb germline-targeting SOSIP immunization compared to that in older monkeys. Aim 2 will
test the hypothesis that the initiation of HIV B cell lineage vaccination in early life compared to preadolescence
will result in antibody maturation that will translate into enhanced protective vaccine efficacy against HIV
acquisition prior to sexual debut. Finally, Aim 3 will test the hypothesis that early life immunologic and
microbiologic signatures predict the development of HIV-neutralizing responses to SOSIP vaccination by
working with the Program's Integrated Systems Immunology Core, to assess the transcriptomic and
microbiome signatures that associated with the induction of bnAb precursor and tier 2 virus neutralization
responses. Furthermore, to establish translatability, we will compare the overall kinetics of vaccine-elicited
somatic hypermutation in U.S and Malawian infants to that of infant monkeys. Taken together, the results of
this Project will provide critical information about age-specific vaccine-elicited immune responses relevant to
refining HIV Env vaccine strategies that take advantage of immune developme...

## Key facts

- **NIH application ID:** 9893372
- **Project number:** 2P01AI117915-06
- **Recipient organization:** DUKE UNIVERSITY
- **Principal Investigator:** Sallie R. Permar
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $244,720
- **Award type:** 2
- **Project period:** — → 2020-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9893372

## Citation

> US National Institutes of Health, RePORTER application 9893372, Project 1: Age-related impact on early life B cell lineage-designed SOSIP HIV Env vaccination (2P01AI117915-06). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9893372. Licensed CC0.

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